This Program will bring the research efforts of a group of investigators to bear on problems concerning the normal and diseased heart and circulation, and aspects of experimental lung disease. The areas of research will encompass investigations on the mechanical properties of myocardium; the mechanisms of adaptation of the whole heart to acute and chronic forms of experimental disease and stress; the ultrastructure of normal and diseased heart muscle; the chronic effects of cardiovascular drugs on cardiac performance; characterization of the functional and metabolic properties of the fetal and neonatal heart; the energetics of the coronary circulation under abnormal conditions; the hormonal regulation of lipolysis and triglyceride uptake from lipoproteins at the cellular level; the biochemical modulation of myocardial contractility under normal and abnormal circumstances; the biochemistry of the sympathetic nervous system relative to mechanisms involving cyclic AMP and the role of calcium; models for the beta adrenergic receptor; structure-function correlations in the pulmonary vascular bed, studies on mechanical properties of the lung, and alterations in hemoglobin dissociation; clinical assessment of ventricular function by invasive and non-invasive methods; and studies on the reversibility of myocardial abnormalities following cardiac operations. Collaborative efforts involving both Research and Core Units have evolved within the broad interdisciplinary base of this Program, and the proposed research should continue to enrich the undergraduate and graduate training programs of this medical school. The techniques of physiology, biochemistry, pharmacology, electron- microscopy, pathology, radiology, and clinical cardiology will be employed in these investigations, which ultimately should provide a more basic understanding of diseases which effect the heart and circulation of man.